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Molecular Pharmacology

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Research ArticleArticle

6-Mercaptopurine Decreases the Bcl-2/Bax Ratio and Induces Apoptosis in Activated Splenic B Lymphocytes

Sonsoles Hortelano and Lisardo Boscá
Molecular Pharmacology March 1997, 51 (3) 414-421;
Sonsoles Hortelano
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Lisardo Boscá
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This article has a correction. Please see:

  • Correction to “6-Mercaptopurine Decreases the Bcl-2/Bax Ratio and Induces Apoptosis in Activated Splenic B Lymphocytes” - October 01, 2017

Abstract

6-Mercaptopurine and related purine antimetabolites are used in the treatment of several B cell disorders. These drugs inhibited the proliferation of mature splenic B cells after being triggered with polyclonal mitogens. In addition to the antiproliferative effects, 6-mercaptopurine, 2-mercaptopurine, and aminoguanidine evoked a rapid apoptotic cell death in activated B cells that started at 6 hr after drug treatment and therefore preceded DNA synthesis. Incubation of activated B lymphocytes with 6-mercaptopurine blocked the low but sustained nitric oxide release observed in these cells that contributes to the prevention of apoptotic cell death; the addition of chemical nitric oxide donors significantly antagonized the apoptosis elicited by these drugs. The inhibition of nitric oxide synthesis elicited by mercaptopurines correlated with a decrease in the release of nitric oxide-derived species to the culture medium and in the intracellular levels of cGMP. The ratio between the amounts of Bcl-2 and Bax, two proteins involved in the control of apoptosis in mature B cells, markedly decreased as result of mercaptopurine treatment.

Footnotes

  • Send reprint requests to: Dr. Lisardo Boscá, Instituto de Bioquimica, Facultad de Farmacia, 28040 Madrid, Spain. E-mail: boscal{at}eucmax.sim.ucm.es

  • This work was supported by Comisión Interministerial de Ciencia y Técnologica Grant PM95–007 and Comunidad de Madrid Grant C183–91. S.H. was supported by a fellowship from Comunidad de Madrid, Spain.

  • Abbreviations:
    MP
    mercaptopurine
    ISO
    dinitrate isosorbide
    LPS
    lipopolysaccharide
    NOS
    nitric oxide synthase
    NO
    nitric oxide
    SIN-I
    3-morpholinosydnonimine
    ELISA
    enzyme-linked immunosorbent assay
    mAb
    monoclonal antibody
    PBS
    phosphate-buffered saline
    • Received July 22, 1996.
    • Accepted November 12, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology
Vol. 51, Issue 3
1 Mar 1997
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Research ArticleArticle

6-Mercaptopurine Decreases the Bcl-2/Bax Ratio and Induces Apoptosis in Activated Splenic B Lymphocytes

Sonsoles Hortelano and Lisardo Boscá
Molecular Pharmacology March 1, 1997, 51 (3) 414-421;

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Research ArticleArticle

6-Mercaptopurine Decreases the Bcl-2/Bax Ratio and Induces Apoptosis in Activated Splenic B Lymphocytes

Sonsoles Hortelano and Lisardo Boscá
Molecular Pharmacology March 1, 1997, 51 (3) 414-421;
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